LAUSR

OBJECTIVE A better understanding of the genetic, molecular and cellular mechanisms of BDNF and its association with neuroplasticity could play a pivotal role in finding future therapeutic targets for novel drugs in major depressive disorder (MDD). Because there are conflicting results regarding the exact role of BDNF polymorphisms in MDD still, we set out to systematically review the current evidence regarding BDNF-related mutations in MDD. METHODS We conducted a keyword-guided search of the PubMed and Embase databases, using "BDNF" or "brain derived neurotrophic factor" and "major depressive disorder" and "single nucleotide polymorphism". We included all publications in line with our exclusion and inclusion criteria that focused on BDNF-related mutations in the context of MDD. RESULTS Our search yielded 427 records in total. After screening and application of our eligibility criteria, 71 studies were included in final analysis. According to present overall scientific data, there is a possibly major pathophysiological role for BDNF neurotrophic systems to play in MDD. However, on the one hand, the synthesis of evidence makes clear that likely no overall association of BDNF-related mutations with MDD exists. On the other hand, it can be appreciated that solidifying evidence emerged on specific significant sub-conditions and stratifications based upon various demographic, clinico-phenotypical and neuromorphological variables. CONCLUSIONS Further research should elucidate specific BDNF-MDD associations based on demographic, clinico-phenotypical and neuromorphological variables. Furthermore, biomarker approaches, specifically combinatory ones, involving BDNF should be further investigated.